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Am J Physiol Endocrinol Metab 272: E461-E468, 1997;
0193-1849/97 $5.00
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AJP - Endocrinology and Metabolism, Vol 272, Issue 3 E461-E468, Copyright © 1997 by American Physiological Society


ARTICLES

Endothelin stimulates osteoblastic production of IL-6 but not macrophage colony-stimulating factor

S. L. Perkins, E. Sarraj, S. J. Kling and D. E. Kohan
Department of Pathology, University of Utah Health Sciences Center, Salt Lake City 84132, USA.

Endothelins (ET) are vasoactive polypeptide hormones that stimulate osteoblastic signal transduction events. Using MC3T3-E1 and primary osteoblasts, we studied ET effects on interleukin-6 (IL-6) and macrophage colony-stimulating factor (M-CSF) production. Enzyme-linked immunosorbent assay analysis showed a dose-dependent 3- to 3.5-fold increase in IL-6 with 100 nM ET-1 stimulation within 4 (primary osteoblasts) to 8 (MC3T3-E1) h. ET-3 was less effective at enhancing IL-6 production, with a maximal twofold increase after 100 nM ET-3 after 4 h. No significant increase in M-CSF production was noted with ET-1 or ET-3 in either cell type. Reverse-transcriptase polymerase chain reaction analysis demonstrated both ET(A) and ET(B) receptors on primary osteoblasts and only ET(A) receptors on MC3T3-E1. ET-1-stimulated IL-6 production was blocked by the inhibitor BQ-123, implicating ET(A) receptor involvement. Increased IL-6 protein was coupled with elevated IL-6 mRNA levels and a twofold increase in IL-6 message half-life.


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Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
Y. Hiruma, A. Inoue, A. Shiohama, E. Otsuka, S. Hirose, A. Yamaguchi, and H. Hagiwara
Endothelins inhibit the mineralization of osteoblastic MC3T3-E1 cells through the A-type endothelin receptor
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1998; 275(4): R1099 - R1105.
[Abstract] [Full Text] [PDF]




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